Journal article
Local Impermeant Anions Establish the Neuronal Chloride Concentration
Science (American Association for the Advancement of Science), Vol.343(6171), pp.670-675
02/07/2014
DOI: 10.1126/science.1245423
PMCID: PMC4220679
PMID: 24503855
Abstract
Neuronal intracellular chloride concentration [Cl(-)](i) is an important determinant of γ-aminobutyric acid type A (GABA(A)) receptor (GABA(A)R)-mediated inhibition and cytoplasmic volume regulation. Equilibrative cation-chloride cotransporters (CCCs) move Cl(-) across the membrane, but accumulating evidence suggests factors other than the bulk concentrations of transported ions determine [Cl(-)](i). Measurement of [Cl(-)](i) in murine brain slice preparations expressing the transgenic fluorophore Clomeleon demonstrated that cytoplasmic impermeant anions ([A](i)) and polyanionic extracellular matrix glycoproteins ([A](o)) constrain the local [Cl(-)]. CCC inhibition had modest effects on [Cl(-)](i) and neuronal volume, but substantial changes were produced by alterations of the balance between [A](i) and [A](o). Therefore, CCCs are important elements of Cl(-) homeostasis, but local impermeant anions determine the homeostatic set point for [Cl(-)], and hence, neuronal volume and the polarity of local GABA(A)R signaling.
Details
- Title: Subtitle
- Local Impermeant Anions Establish the Neuronal Chloride Concentration
- Creators
- J Glykys - Department of Neurology. Massachusetts General Hospital, Harvard Medical School, Boston, MAV Dzhala - Department of Neurology. Massachusetts General Hospital, Harvard Medical School, Boston, MAK Egawa - Department of Neurology. Massachusetts General Hospital, Harvard Medical School, Boston, MAT Balena - Department of Neurology. Massachusetts General Hospital, Harvard Medical School, Boston, MAY Saponjian - Department of Neurology. Massachusetts General Hospital, Harvard Medical School, Boston, MAK V Kuchibhotla - NYU School of Medicine, Skirball Institute for Biomolecular MedicineB J Bacskai - Department of Neurology. Massachusetts General Hospital, Harvard Medical School, Boston, MAK T Kahle - Department of Neurosurgery. Massachusetts General Hospital, Harvard Medical School, Boston, MAT Zeuthen - Department of Cellular and Molecular Medicine, University of CopenhagenK J Staley - Department of Neurology. Massachusetts General Hospital, Harvard Medical School, Boston, MA
- Resource Type
- Journal article
- Publication Details
- Science (American Association for the Advancement of Science), Vol.343(6171), pp.670-675
- DOI
- 10.1126/science.1245423
- PMID
- 24503855
- PMCID
- PMC4220679
- NLM abbreviation
- Science
- ISSN
- 0036-8075
- eISSN
- 1095-9203
- Language
- English
- Date published
- 02/07/2014
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9984020651602771
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